1. Field of the Invention
The invention relates to phototherapy, wherein a drug delivery system is used to target cells of a specific kind in a selected organ or part of the body, even when the cells are not specific or sufficiently specific to the location.
2. Invention Disclosure Statement
Drug therapies need to be increasingly selective to avoid side effects. It is beneficial for drugs that are administered systemically to target only specific cells in selective locations, and thus avoid harmful effects on normal cells in the rest of the body.
To achieve this goal, different methods have been attempted. Vectors, such as lectins, selecting, antibodies have been developed and coupled to therapeutic agents to accomplish this selectivity. For example, U.S. Pat. No. 4,671,958(J. Rodwell and T. McKearn) described a method for delivering of compounds to target sites by conjugating the compounds to antibodies. When such compound-antibody complexes are administered to a patient, the antibody binds to desired target antigen, such as certain tumor cells, in vivo. This antigen-antibody reaction will trigger the patient""s serum complement system, and attached compounds will be cleaved off by the proteolytic enzymes of the complement system and become active. However, since an antibody will bind to its counterpart antigen existing anywhere in the body, this method fails to achieve the desired selectivity when the antigenic cells are not particularly specific to a selected organ or part of a body.
Another attempt has been made using photoactivation. In this method, a drug is activated by radiation in the desired local area. For example, U.S. Pat. No. 4,590,211(J. Voorhees et al) describes a method comprising the administration of a pro-drug to a patient. A pro-drug is formed by a therapeutic compound chemically combined with another moiety by a photocleavable bond and the combination is inactive. Subsequent ultraviolet radiation of the diseased area will cleave the photocleavable bond and release the therapeutic compound. U.S. Pat. No. 4,086,254 (W. Wierenga) describes new compounds that have a photocleavable group removable by irradiation. The compounds have reduced activity in the uncleaved state and provide a therapeutically active compound upon irradiation at the desired site. However, the photoactivation method used in these patents has certain limits. The drug, which is delivered in this way, does not bind to any specific cells or particular antigens. Therefore, they do not achieve the cell-specific effect in a particular organ. Generally, such systems are used only to treat the inflammatory and/or proliferative skin diseases.
The present invention provides a system that delivers compounds to specific cells in selected organs or part of a body by using photoselective markers.
It is an object of the present invention to provide a system that delivers therapeutic compounds to particular cells in selected organs, thereby preventing potential harmful side effects of such compounds on the normal cells in the rest of the body.
It is another object of the present invention to use a vector component that will target a specific site or particular cells such that the connected therapeutic compounds will be delivered to the site or cells.
Still another object of the present invention is to use a marker component complexed to the vector component, and still capable of being targeted by therapeutic/diagnostic agents or components of the immune system.
Yet another object of the present invention is to use a cap component connected to the marker component by a photocleavable bond or a photosensitive bond, so that radiation in a desirable site cleaves the cap component off and render the marker component available for binding to a therapeutic or diagnostic agent or a component of the immune system.
It is a further object of the present invention to direct therapeutic/diagnostic agents or components of the immune system only at a desired site or organ through the specific interaction of the marker component and the therapeutic or diagnostic agents/components.
Briefly stated, the present invention provides a drug delivery system wherein a therapeutic/diagnostic agent or a component of the immune system is directed to particular cells in a selected organ or a specific site. Such a system can be formed by a photoselective compound generally described as V-M-P-C. V is a vector component suitable to target particular cells in a selected organ or site, where the type of the cell or antigen does not have to be specific to the desired treatment site. M is a marker component that is capable of being targeted by a therapeutic/diagnostic agent or a component of the immune system. P is a photocleavable or photosensitive bond, and C is a cap component rendering M ineffective. C is connected to M by the photocleavable or photosensitive bond. The photoselective compound is administered and marks targets of a certain kind of cell or a specific site. Then radiation of a specific wavelength or wavelength range is applied to the geometric volume that is to be treated, uncapping the M sites in the desired treatment volume. Therapeutic or diagnostic agents can be subsequently or concurrently administered in a form that specifically targets the uncapped sites of M. The therapeutic or diagnostic agent can be a drug, a radioactive compound, a fluorescent compound or a photosensitiser. Additional components, such as multiplier molecules, can also be inserted into the basic V-M-P-C scheme. Moreover, the marker component can be such that after the removal of the cap component, components of the immune system can bind to M and thus concentrate at a desired site. The present invention facilitates the delivery of therapeutic/diagnostic agents or components of the immune system to particular cells in a selected organ or a specific site, and therefore, minimizes the potential harmful effect of the agents to the normal cells in the rest of the body.